eprintid: 1329816 rev_number: 48 eprint_status: archive userid: 608 dir: disk0/01/32/98/16 datestamp: 2011-11-09 06:11:00 lastmod: 2021-10-04 01:40:55 status_changed: 2011-11-09 06:10:59 type: article metadata_visibility: show item_issues_count: 0 creators_name: Tulone, C creators_name: Sponaas, AM creators_name: Raiber, EA creators_name: Tabor, AB creators_name: Langhorne, J creators_name: Chain, BM title: Differential requirement for cathepsin D for processing of the full length and C-terminal fragment of the malaria antigen MSP1. ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D15 divisions: B04 divisions: C06 divisions: F56 keywords: Animals, Antibody Formation, Antigen Presentation, Antigens, Protozoan, Bone Marrow Cells, Cathepsin D, Chimera, Dendritic Cells, Erythrocytes, Histocompatibility Antigens Class II, Immunoglobulin G, Malaria, Merozoite Surface Protein 1, Merozoites, Mice, Parasitemia, Phenotype, Plasmodium chabaudi, Protease Inhibitors, Spleen note: © 2011 Tulone et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The study was supported by the Biotechnology and Biological Sciences Research Council (BB/D005469/1) under the Selective Chemical Intervention in Biological Systems initiative and by the Medical Research Council, United Kingdom, ref. U117584248. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. abstract: Merozoite Surface Protein 1 is expressed on the surface of malaria merozoites and is important for invasion of the malaria parasite into erythrocytes. MSP1-specific CD4 T cell responses and antibody can confer protective immunity in experimental models of malaria. In this study we explore the contributions of cathepsins D and E, two aspartic proteinases previously implicated in antigen processing, to generating MSP1 CD4 T-cell epitopes for presentation. The absence of cathepsin D, a late endosome/lysosomal enzyme, is associated with a reduced presentation of MSP1 both following in vitro processing of the epitope MSP1 from infected erythrocytes by bone marrow-derived dendritic cells, and following in vivo processing by splenic CD11c+ dendritic cells. By contrast, processing and presentation of the soluble recombinant protein fragment of MSP1 is unaffected by the absence of cathepsin D, but is inhibited when both cathepsin D and E are absent. The role of different proteinases in generating the CD4 T cell repertoire, therefore, depends on the context in which an antigen is introduced to the immune system. date: 2011-10-28 official_url: http://dx.doi.org/10.1371/journal.pone.0024886 vfaculties: VGHCSCI vfaculties: VMPS oa_status: green pmcid: PMC3203867 language: eng primo: open primo_central: open_green article_type_text: Journal Article, Research Support, Non-U.S. Gov't verified: verified_manual elements_source: PubMed elements_id: 348795 doi: 10.1371/journal.pone.0024886 pii: PONE-D-11-03765 lyricists_name: Chain, Benjamin lyricists_name: Tabor, Alethea lyricists_id: BMCHA43 lyricists_id: ABTAB91 full_text_status: public publication: PLOS One volume: 6 number: 10 article_number: e24886 event_location: United States issn: 1932-6203 citation: Tulone, C; Sponaas, AM; Raiber, EA; Tabor, AB; Langhorne, J; Chain, BM; (2011) Differential requirement for cathepsin D for processing of the full length and C-terminal fragment of the malaria antigen MSP1. PLOS One , 6 (10) , Article e24886. 10.1371/journal.pone.0024886 <https://doi.org/10.1371/journal.pone.0024886>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1329816/1/1329816.pdf